Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample

Bipolar disorder (BD) often presents with a broad range of symptoms, but there is little agreement as to the heritability and genetic relationships between dimensional and categorical models of this often-disabling disorder.Participants in the Amish-Mennonite Bipolar Genetics (AMBiGen) study, which enrolls families with BD and related disorders from Amish and Mennonite communities in North and South America, were assigned a categorical mood disorder diagnosis by structured psychiatric interview and asked to complete the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of cardinal manic symptoms and associated impairment. Principal Component Analysis (PCA) was performed to analyze the dimensions of the MDQ in 726 participants, 212 of whom carried a categorical diagnosis of major mood disorder. SOLAR-ECLIPSE (v9.0.0) was used to estimate heritability and genetic overlaps between MDQ-derived measures and categorical diagnoses among 432 genotyped participants.As expected, MDQ scores were significantly higher among individuals diagnosed with BD and related disorders. PCA suggested a three-component model for the MDQ, consistent with the literature. Heritability of the MDQ symptom score was estimated at 30% (p<0.001), which was evenly distributed across its three principal components. Strong and significant genetic correlations were found between categorical diagnoses and most MDQ measures, especially impairment.The results support the MDQ as a dimensional measure of BD. Furthermore, significant heritability and high genetic correlations between MDQ scores and categorical diagnoses suggest a genetic continuity between dimensional and categorical measures of major mood disorders.